The Oncology QCARD Initiative: Fostering efficient evaluation of initial real-world data proposals.

PURPOSE: The oncology quality, characterization, and assessment of real-world data (Oncology QCARD) Initiative was formed to develop a set of minimum study design and data elements needed to evaluate the fitness of the real-world data (RWD) source(s) proposed in an initial study concept as part of early interaction with scientific reviewers. METHODS: A multidisciplinary executive committee (EC) was established to guide the Oncology QCARD Initiative. The EC conducted a landscape review of published literature, guidances, and guidelines to evaluate relevant dimensions of data quality measurement. Guided by the review and informed by expert feedback, the Oncology QCARD Initial Protocol Characterization (IPC) provides a summary of minimum elements needed to adequately describe an initial clinical study concept that involves RWD and is intended to support decision-making. RESULTS: Fit-for-use data and fit-for-purpose design emerged as themes from the landscape analysis. Data that are fit-for-use are both relevant (sufficiently capturing exposure, outcomes, and covariates) and reliable (understanding data accrual and quality control and whether the data represent the underlying concepts they are intended to represent) to answer a specific research question. A fit-for-purpose design takes appropriate steps to ensure internal and external validity and allows for transparency in reporting. The QCARD-IPC focuses on high-level characteristics of RWD sources and study design domains including data temporality, population, medical product exposure, comparators, and covariates, endpoints, statistical analysis, and data quality assurance plans. CONCLUSIONS: Evaluation of studies including RWD requires understanding the data source, study design, and potential biases to preliminarily evaluate whether selected RWD are fit-for-use for the research question. The Oncology QCARD-IPC provides a structured, transparent approach to facilitate early review and enhanced communication between study sponsors and scientific reviewers of initial study proposals including RWD.

2,4-D exposure and urinary markers of oxidative DNA damage and lipid peroxidation: a longitudinal study.

OBJECTIVE: 2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide that is commonly used commercially, agriculturally and residentially worldwide. There is concern about its potential for carcinogenicity based on studies in laboratory animals demonstrating the potential for induction of oxidative stress. We conducted a longitudinal biomarker study of 31 pesticide applicators in Kansas who heavily applied 2,4-D and 34 non-applicator controls. METHODS: We used multivariable generalised linear mixed-effect models to evaluate the association between urinary 2,4-D and natural log-transformed 8-iso prostaglandin F2α (8-isoprostane) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), adjusting for urinary creatinine, age, tobacco use and concomitant use of the herbicide picloram. RESULTS: Compared with non-applicator controls, urinary 2,4-D in the third quartile of exposure was associated with elevated 8-isoprostane (eß=1.38, 95% CI 1.03 to 1.84). There was no association among the highest exposed and no exposure-response trend. 2,4-D exposure was not associated with 8-OHdG. Results were unchanged when restricted to participants who only applied 2,4-D (no picloram use). CONCLUSIONS: We did not find evidence that increasing 2,4-D exposure was associated with 8-isoprostane or 8-OHdG. Future work should carefully evaluate potential confounders of this association, such as diet and physical activity, as well as additional biological markers of oxidative stress and damage.

Pesticide exposure and risk of aggressive prostate cancer among private pesticide applicators.

BACKGROUND: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men in developed countries; however, little is known about modifiable risk factors. Some studies have implicated organochlorine and organophosphate insecticides as risk factors (particularly the organodithioate class) and risk of clinically significant PCa subtypes. However, few studies have evaluated other pesticides. We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators in North Carolina and Iowa, to extend our previous work and evaluate 39 additional pesticides and aggressive PCa. METHODS: We used Cox proportional hazards models, with age as the time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ever use of individual pesticides and 883 cases of aggressive PCa (distant stage, poorly differentiated grade, Gleason score ≥ 7, or fatal prostate cancer) diagnosed between 1993 and 2015. All models adjusted for birth year, state, family history of PCa, race, and smoking status. We conducted exposure-response analyses for pesticides with reported lifetime years of use. RESULTS: There was an increased aggressive PCa risk among ever users of the organodithioate insecticide dimethoate (n = 54 exposed cases, HR = 1.37, 95% CI = 1.04, 1.80) compared to never users. We observed an inverse association between aggressive PCa and the herbicide triclopyr (n = 35 exposed cases, HR = 0.68, 95% CI = 0.48, 0.95), with the strongest inverse association for those reporting durations of use above the median (≥ 4 years; n = 13 exposed cases, HR=0.44, 95% CI=0.26, 0.77). CONCLUSION: Few additional pesticides were associated with prostate cancer risk after evaluation of extended data from this large cohort of private pesticide applicators.

Cancer incidence in the Agricultural Health Study after 20 years of follow-up.

PURPOSE: To evaluate cancer incidence in the Agricultural Health Study (AHS), a cohort of private pesticide applicators, their spouses, and commercial applicators, based on 12,420 cancers, adding 5,989 cancers, and 9 years of follow-up since last evaluation. METHODS: We calculated age, year, sex, and race-adjusted standardized incidence ratios (SIR) and 95% confidence intervals (CI) for cancer sites in the AHS relative to the general population. RESULTS: Overall AHS cancer incidence was lower than the general population (SIRprivate = 0.91, CI 0.89-0.93; SIRspouse = 0.89, CI 0.86-0.92; SIRcommercial = 0.83, CI 0.76-0.92), with notable deficits across applicators and spouses for oral cavity, pancreas, and lung cancers. Cancer excesses included prostate cancer, lip cancer, certain B-cell lymphomas (e.g., multiple myeloma), acute myeloid leukemia (AML), thyroid cancer, testicular cancer, and peritoneal cancer. The lung cancer deficit was strongest among applicators reporting potential exposure to endotoxin at study enrollment (tasks such as raising animals and handling stored grain). CONCLUSIONS: Although an overall deficit in cancer was observed, there were notable exceptions, including newly observed excesses for AML, thyroid, testicular, and peritoneal cancers. Furthermore, endotoxin exposure may, in part, account for observed lung cancer incidence deficits. Cancer incidence patterns in the AHS suggest farm exposures' relevance to cancer etiology.

Cancer treatment and survivorship statistics, 2012.

Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.

Pesticide use and incident hyperthyroidism in farmers in the Agricultural Health Study.

BACKGROUND: Few studies have evaluated associations between pesticides and hyperthyroidism. OBJECTIVE: We evaluated associations between specific pesticides and incident hyperthyroidism in private pesticide applicators in the Agricultural Health Study. METHODS: We used Cox proportional hazards models to estimate HRs and 95% CIs for associations between pesticide use at enrolment and hyperthyroidism (n=271) in 35 150 applicators (mostly men), adjusting for potential confounders. RESULTS: Ever use of several pesticides (organophosphate insecticide malathion, fungicide maneb/mancozeb, herbicides dicamba, metolachlor, and atrazine in overall sample and chlorimuron ethyl among those ≤62 years) was associated with reduced hyperthyroidism risk, with HRs ranging from 0.50 (95% CI 0.30 to 0.83) for maneb/mancozeb to 0.77 (95% CI 0.59 to 1.00) for atrazine. Hyperthyroidism risk was lowest among those with higher intensity-weighted lifetime days of using carbofuran and chlorpyrifos (ptrend ≤0.05). CONCLUSIONS: Observed associations between pesticides and decreased risk of hyperthyroidism warrant further investigation.

Overall and cause-specific mortality in a cohort of farmers and their spouses.

OBJECTIVES: Lower mortality rates compared with the general population have been reported for Agricultural Health Study (AHS) participants (enrolled 1993-1997) followed through 2007. We extended analysis of mortality among AHS participants (51 502 private pesticide applicators, their 31 867 spouses and 4677 commercial pesticide applicators from North Carolina and Iowa) through 2015 and compared results using several analytical approaches. METHODS: We calculated standardised mortality ratios (SMRs), causal mortality ratios (CMR) and relative SMRs (rSMR) using state-specific mortality rates of the general populations as the referent. RESULTS: Over the average 16 years of follow-up (1999-2015), 9305 private applicators, 3384 spouses and 415 commercial applicators died. SMRs and CMRs, with expected deaths calculated using the person-time among the cohort and the general population, respectively, indicated lower overall mortality in all study subgroups (SMRs from 0.61 to 0.69 and CMRs from 0.74 to 0.89), although CMRs indicated elevated mortality in private applicators from North Carolina and in ever-smokers. In SMR analyses, there were fewer than expected deaths from many causes, but deaths from some external causes including transportation-related injuries and mechanical forces were elevated in private applicators. CMRs indicated higher than expected deaths from prostate cancer, lymphohaematopoietic cancers, Parkinson's and Alzheimer's disease, and chronic glomerulonephritis in private applicators, and non-Hodgkin's lymphoma in spouses (from 1.19 to 1.53). rSMR results were generally elevated, similar to CMR findings. CONCLUSIONS: AHS participants experienced lower overall mortality than the general population.Mortality from a few specific causes was increased in private applicators, specifically when CMR and rSMR approaches were used.

Occupational pesticide exposure and subclinical hypothyroidism among male pesticide applicators.

OBJECTIVES: Animal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. We evaluated the relationship between individual pesticides and thyroid function in 679 men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators. METHODS: Self-reported lifetime pesticide use was obtained at cohort enrolment (1993-1997). Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure (eg, use of personal protective equipment). Thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and antithyroid peroxidase (anti-TPO) autoantibodies were measured in serum collected in 2010-2013. We used multivariate logistic regression to estimate ORs and 95% CIs for subclinical hypothyroidism (TSH >4.5 mIU/L) compared with normal TSH (0.4-<4.5 mIU/L) and for anti-TPO positivity. We also examined pesticide associations with TSH, T4 and T3 in multivariate linear regression models. RESULTS: Higher exposure to the insecticide aldrin (third and fourth quartiles of intensity-weighted days vs no exposure) was positively associated with subclinical hypothyroidism (ORQ3=4.15, 95% CI 1.56 to 11.01, ORQ4=4.76, 95% CI 1.53 to 14.82, ptrend <0.01), higher TSH (ptrend=0.01) and lower T4 (ptrend=0.04). Higher exposure to the herbicide pendimethalin was associated with subclinical hypothyroidism (fourth quartile vs no exposure: ORQ4=2.78, 95% CI 1.30 to 5.95, ptrend=0.02), higher TSH (ptrend=0.04) and anti-TPO positivity (ptrend=0.01). The fumigant methyl bromide was inversely associated with TSH (ptrend=0.02) and positively associated with T4 (ptrend=0.01). CONCLUSIONS: Our results suggest that long-term exposure to aldrin, pendimethalin and methyl bromide may alter thyroid function among male pesticide applicators.

A nested case-control study of polychlorinated biphenyls, organochlorine pesticides, and thyroid cancer in the Janus Serum Bank cohort.

BACKGROUND: Polychlorinated biphenyls (PCBs) and organochlorine pesticides have been associated with altered thyroid hormone levels in humans, but their relationship with thyroid cancer is unknown. METHODS: We conducted a nested case-control study of thyroid cancer in the Norwegian Janus Serum Bank cohort using pre-diagnostic blood samples from 1972 to 1985. Incident thyroid cancer (n = 108) was ascertained through 2008. Controls were matched 2:1 by age, date of blood draw, gender, and county. We used gas chromatography/mass spectrometry to quantify 36 PCB congeners and metabolites of pesticides DDT, chlordane, hexachlorocyclohexane, and hexachlorobenzene. PCBs and pesticide metabolites were evaluated individually and summed by degree of chlorination and parent compound, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression per specified increase in lipid-adjusted concentration. We additionally stratified analyses by birth cohort (1923-1932, 1933-1942, 1943-1957). RESULTS: Increasing concentration of DDT metabolites (ORper 1000 ng/g = 0.80, 95%CI = 0.66-0.98) was inversely associated with thyroid cancer. Associations for PCBs were null or in inverse direction. We observed interactions for total PCBs, moderately-chlorinated PCBs, and chlordane metabolites with birth cohort (p ≤ 0.04). Among participants born 1943-1957, total PCBs (ORper 100 ng/g = 1.25, 95%CI = 1.00-1.56), moderately-chlorinated PCBs (ORper 100 ng/g = 1.31, 95%CI = 1.01-1.70), and chlordane metabolites (ORper 10 ng/g = 1.78, 95%CI = 1.09-2.93) were positively associated with thyroid cancer. For individuals born before 1943, associations were generally null or in the inverse direction. CONCLUSIONS: Emissions of PCBs and OC pesticides varied over time. Different risk patterns by birth cohort suggest the potential importance of timing of exposure in thyroid cancer risk. Further evaluation of these associations is warranted.

Greater Coronary Heart Disease Risk With Lower Intensity and Longer Duration Smoking Compared With Higher Intensity and Shorter Duration Smoking: Congruent Results Across Diverse Cohorts.

INTRODUCTION: Relative risks (RRs) for coronary heart disease (CHD) by cigarettes/day exhibit a concave pattern, implying the RR increase with each additional cigarette/day consumed decreases with greater intensity. Interpreting this pattern faces limitations, since cigarettes/day alone does not fully characterize smoking-related exposure. A more complete understanding of smoking and CHD risk requires a more comprehensive representation of smoking. METHODS: Using Poisson regression, we applied a RR model in pack-years and cigarettes/day to analyze two diverse cohorts, the US Agricultural Health Study, with 4396 CHD events and 1 425 976 person-years of follow-up, and the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, with 5979 CHD events and 486 643 person-years. RESULTS: In both cohorts, the concave RR pattern with cigarettes/day was consistent with cigarettes/day modifying a linear RR association for CHD by pack-years within categories of cigarettes/day, indicating that strength of the pack-years association depended on cigarettes/day (p < .01). For example, at 50 pack-years (365 000 total cigarettes), estimated RRs of CHD were 2.1 for accrual at 20 cigarettes/day and 1.5 for accrual at 50 cigarettes/day. CONCLUSIONS: RRs for CHD increased with pack-years with smoking intensities affecting the strength of association. For equal pack-years, smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration. We have now observed inverse smoking intensity effects in multiple cohorts with differing smoking patterns and other characteristics, suggesting a common underlying phenomenon. IMPLICATIONS: Risk of CHD increases with pack-years of smoking, but accrual intensity strongly influences the strength of the association, such that smoking fewer cigarettes/day for longer duration is more deleterious than smoking more cigarettes/day for shorter duration. This observation offers clues to better understanding biological mechanisms, and reinforces the importance of cessation rather than smoking less to reduce CHD risk.

Occupational exposure to pesticides and other biocides and risk of thyroid cancer.

OBJECTIVES: To assess the associations between occupational exposure to biocides and pesticides and risk of thyroid cancer. METHODS: Using data from a population-based case-control study involving 462 incident thyroid cancer cases and 498 controls in Connecticut collected in 2010-2011, we examined the association with occupational exposure to biocides and pesticides through a job-exposure matrix. We used unconditional logistic regression models to estimate OR and 95% CI, adjusting for potential confounders. RESULTS: Individuals who were occupationally ever exposed to biocides had an increased risk of thyroid cancer (OR=1.65, 95% CI 1.16 to 2.35), and the highest risk was observed for the high cumulative probability of exposure (OR=2.18, 95% CI 1.28 to 3.73). The observed associations were similar when we restricted to papillary thyroid cancer and well-differentiated thyroid cancer. Stronger associations were observed for thyroid microcarcinomas (tumour size ≤1 cm). No significant association was observed for occupational exposure to pesticides. CONCLUSIONS: Our study provides the first evidence linking occupational exposure to biocides and risk of thyroid cancer. The results warrant further investigation.

A prospective study of cancer risk among Agricultural Health Study farm spouses associated with personal use of organochlorine insecticides.

BACKGROUND: Organochlorine insecticides (OCs) have historically been used worldwide to control insects, although most have now been banned in developed countries. Evidence for an association between OC exposures and cancer predominantly comes from occupational and population based-studies among men. We evaluated the association between the use of specific OCs and cancer among the female spouses of pesticide applicators in the Agricultural Health Study. METHODS: At enrollment (1993-1997), spouses of private applicators in the cohort provided information about their own use of pesticides, including seven OCs (aldrin, chlordane, dieldrin, DDT, heptachlor, lindane, and toxaphene), and information on potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for cancers (n ≥ 3 exposed cases) reported to state cancer registries from enrollment through 2012 (North Carolina) and 2013 (Iowa), and use of the individual OCs, as well as use of any of the specific OCs. RESULTS: Among 28,909 female spouses, 2191 (7.58%) reported ever use of at least one OC, of whom 287 were diagnosed with cancer. Most cancers were not associated with OC use. Risk of glioma was increased among users of at least one OC (Nexposed = 11, RR = 3.52, 95% CI 1.72-7.21) and specifically among lindane users (Nexposed = 3, RR = 4.45, 95% CI 1.36-14.55). Multiple myeloma was associated with chlordane (Nexposed = 6, RR = 2.71, 95% CI 1.12-6.55). Based on 3 exposed cases each, there were also positive associations between pancreatic cancer and lindane, and ER-PR- breast cancer and dieldrin. No other associations with breast cancer were found. CONCLUSIONS: Overall, there were some associations with OC use and cancer incidence, however we were limited by the small number of exposed cancer cases. Future research should attempt to expand on these findings by assessing environmental sources of OC exposures, to fully evaluate the role of OC exposures on cancer risk in women.

Folic acid supplementation, dietary folate intake and risk of preterm birth in China.

PURPOSE: Folic acid supplementation has been suggested to reduce the risk of preterm birth. However, results from previous epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake during pre- and post-conception reduces the risk of preterm birth. METHODS: We analyzed data from a birth cohort study conducted between 2010 and 2012 in Lanzhou, China, including 10,179 pregnant women with live singleton births. RESULTS: Compared to non-users, folic acid supplement users with >12-week duration had a reduced risk of preterm birth (OR 0.67, 95 % CI 0.55-0.83) with a significant dose-response relationship (P for trend = 0.01). A similar pattern was observed for spontaneous preterm birth. Stronger associations were seen for ever use of folic acid supplement and very preterm birth (OR 0.50, 95 % CI 0.36-0.69) and spontaneous very preterm birth (OR 0.42, 95 % CI 0.29-0.63). Dietary folate intake during preconception and pregnancy were also associated with reduced risk of preterm birth (OR 0.68, 95 % CI 0.56-0.83, OR 0.57, 95 % CI 0.47-0.70 for the highest quartiles, respectively), particularly for spontaneous very preterm (OR 0.41, 95 % CI 0.24-0.72, OR 0.26, 95 % CI 0.15-0.47 for the highest quartiles, respectively). There were also decreased risks of preterm birth observed per 10-µg increase in dietary folate intake, and similar associations were found after stratification by folic acid supplementation status. CONCLUSIONS: Our results suggest that folic acid supplementation and higher dietary folate intake during preconception and pregnancy reduces the risk of preterm birth, and the protective effect varies by preterm subtypes.

Maternal tea consumption and the risk of preterm delivery in urban China: a birth cohort study.

BACKGROUND: Studies investigating the relationship between maternal tea drinking and risk of preterm birth have reached inconsistent results. METHODS: The present study analyzed data from a birth cohort study including 10,179 women who delivered a singleton live birth were conducted in Lanzhou, China between 2010 and 2012. RESULTS: Drinking tea (OR = 1.36, 95 % CI: 1.09-1.69), and specifically green (OR = 1.42, 95 % CI: 1.08-1.85) or scented tea (OR = 1.61, 95 % CI: 1.04-2.50), was associated with an increased risk of preterm birth. Drinking tea was associated with both moderate preterm (OR = 1.41, 95 % CI: 1.12-1.79) and spontaneous preterm birth (OR = 1.41, 95 % CI: 1.09-1.83). Risk of preterm birth increased with decreasing age of starting tea drinking (<20 years, OR = 1.60, 95 % CI: 1.17-2.20) and increasing duration (p for trend < 0.01). The relationship between tea drinking and preterm birth is modified by both maternal age (p < 0.05) and gestational weight gain (p < 0.05). CONCLUSIONS: Despite conflicting findings in the previous literature, we saw a significant association with maternal tea drinking and risk of preterm birth in our cohort. More studies are needed both to confirm this finding and to elucidate the mechanism behind this association.

Use of Dietary Vitamin Supplements and Risk of Thyroid Cancer: A Population-Based Case-Control Study in Connecticut.

Certain dietary supplements have been reported to increase the risk of some cancers. Over half of the US population regularly uses dietary supplements. Thyroid cancer incidence has increased over the past several decades. However, few studies have investigated the association between dietary supplements and thyroid cancer. Thus, it is essential to clarify any association between dietary supplements and risk of thyroid cancer. MATERIALS AND METHODS: A population-based case-control study in Connecticut was conducted during 2010-2011 among 462 histologically confi rmed incident thyroid cancer cases and 498 population-based controls. Dietary supplement intake was ascertained through in-person interviews and a food frequency questionnaire. Multivariate unconditional logistic regression models were used to estimate the risk of thyroid cancer and dietary supplement use. RESULTS: Overall, no statistically signifi cant associations were observed between dietary supplementation and thyroid cancer risk. Stratifi ed analyses revealed a suggestive protective effect on risk of papillary microcarcinoma among longterm (> 10 years) use of multivitamins (OR = 0.59, 95 % CI: 0.33, 1.04) and calcium supplementation (OR = 0.45, 95 % CI: 0.22, 0.93). An increased risk of large papillary thyroid cancers (tumor size > 1 cm) was observed among short-term (< 5 years) users of calcium supplements (OR = 2.24, 95 % CI: 1.30, 3.88). DISCUSSION: No signifi cant associations were observed between supplementation and overall thyroid cancer risk. The different associations between calcium supplements and risk of papillary thyroid cancer by tumor size warrant further investigation.

Use of acetochlor and cancer incidence in the Agricultural Health Study.

Since its registration in 1994 acetochlor has become a commonly used herbicide in the US, yet no epidemiologic study has evaluated its carcinogenicity in humans. We evaluated the use of acetochlor and cancer incidence among licensed pesticide applicators in the Agricultural Health Study. In telephone interviews administered during 1999-2005, participants provided information on acetochlor use, use of other pesticides and additional potential confounders. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (95% CI) for cancers that occurred from the time of interview through 2011 in Iowa and 2010 in North Carolina. Among 33,484 men, there were 4,026 applicators who used acetochlor and 3,234 incident cancers, with 304 acetochlor-exposed cases. Increased risk of lung cancer was observed among acetochlor users (RR = 1.74; 95% CI: 1.07-2.84) compared to nonusers, and among individuals who reported using acetochlor/atrazine product mixtures (RR = 2.33; 95% CI: 1.30-4.17), compared to nonusers of acetochlor. Colorectal cancer risk was significantly elevated among the highest category of acetochlor users (RR = 1.75; 95% CI: 1.08-2.83) compared to never users. Additionally, borderline significantly increased risk of melanoma (RR = 1.61; 95% CI: 0.98-2.66) and pancreatic cancer (RR = 2.36; 95% CI: 0.98-5.65) were observed among acetochlor users. The associations between acetochlor use and lung cancer, colorectal cancer, melanoma and pancreatic cancer are suggestive, however the lack of exposure-response trends, small number of exposed cases and relatively short time between acetochlor use and cancer development prohibit definitive conclusions.

Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study.

OBJECTIVES: Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. METHODS: At enrolment (1993-1997), spouses provided information about ever use of specific pesticides, including 10 OPs, demographic information, reproductive health history and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% CIs for all cancers diagnosed through 2010 for North Carolina and through 2011 for Iowa. RESULTS: Among 30,003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43). CONCLUSIONS: We observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.

Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis.

OBJECTIVE: Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS. METHODS: Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993-1997) and follow-up (1998-2005); cancer incidence was assessed through 2010(North Carolina)/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with ≥10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure). RESULTS: We observed elevated lung cancer risks (N=283) among applicators with the greatest number of LT (RR=1.60; 95% CI 1.11 to 2.31; P(trend)=0.02) and IW days of diazinon use (RR=1.41; 95% CI 0.98 to 2.04; P(trend)=0.08). Kidney cancer (N=94) risks were non-significantly elevated (RR(LT) days=1.77; 95% CI 0.90 to 3.51; P(trend)=0.09; RR(IW) days 1.37; 95% CI 0.64 to 2.92; P(trend)=0.50), as were risks for aggressive prostate cancer (N=656). CONCLUSIONS: Our updated evaluation of diazinon provides additional evidence of an association with lung cancer risk. Newly identified links to kidney cancer and associations with aggressive prostate cancer require further evaluation.

Exposure to cooking fuels and birth weight in Lanzhou, China: a birth cohort study.

BACKGROUND: Early studies have suggested that biomass cooking fuels were associated with increased risk of low birth weight (LBW). However it is unclear if this reduced birth weight was due to prematurity or intrauterine growth restriction (IUGR). METHODS: In order to understand the relationship between various cooking fuels and risk of LBW and small for gestational age (SGA), we analyzed data from a birth cohort study conducted in Lanzhou, China which included 9,895 singleton live births. RESULTS: Compared to mothers using gas as cooking fuel, significant reductions in birth weight were observed for mothers using coal (weight difference = 73.31 g, 95 % CI: 26.86, 119.77) and biomass (weight difference = 87.84 g, 95 % CI: 10.76, 164.46). Using biomass as cooking fuel was associated with more than two-fold increased risk of LBW (OR = 2.51, 95 % CI: 1.26, 5.01), and the risk was mainly seen among preterm births (OR = 3.43, 95 % CI: 1.21, 9.74). No significant associations with LBW were observed among mothers using coal or electromagnetic stoves for cooking. CONCLUSIONS: These findings suggest that exposure to biomass during pregnancy is associated with risk of LBW, and the effect of biomass on LBW may be primarily due to prematurity rather than IUGR.

Passive smoking and preterm birth in urban China.

Studies investigating the relationship between maternal passive smoking and the risk of preterm birth have reached inconsistent conclusions. A birth cohort study that included 10,095 nonsmoking women who delivered a singleton live birth was carried out in Lanzhou, China, between 2010 and 2012. Exposure to passive smoking during pregnancy was associated with an increased risk of very preterm birth (<32 completed weeks of gestation; odds ratio = 1.98, 95% confidence interval: 1.41, 2.76) but not moderate preterm birth (32-36 completed weeks of gestation; odds ratio = 0.98, 95% confidence interval: 0.81, 1.19). Risk of very preterm birth increased with the duration of exposure (P for trend = 0.0014). There was no variability in exposures by trimester. The associations were consistent for both medically indicated and spontaneous preterm births. Overall, our findings support a positive association between passive smoking and the risk of very preterm birth.